title: Intensive combined modality therapy including low-dose TBI in high-risk Ewing's Sarcoma Patients.
abstract: Twenty-four high-risk Ewing's sarcoma patients were treatedf on an intensive combined modality protocol including low-dose fractionated total body irradiation (TBI) and autologous bone marrow infusion (ABMI). Twenty patients (83%) achieved a complete clinical response to the primary and/or metastatic sites following induction therapy. The median disease-free interval was 18 months, and nine patients remain disease-free with a follow-up of 22 to 72 months. Local failure as a manifestation of initial relapse occurred in only three patients (15%), each having synchronous distant failure. Eight patients failed initially with only distant metastases, usually within 1-2 years following a complete clinical response. Two patients with a single metastasis were again rendered disease-free and remain free from second relapse with 18 and 30 months follow-up. No other relapsed patient was able to be rendered disease-free, and most died of progressive disease within 6 to 12 months of relapse. Two patterns of granulocyte recovery following consolidative therapy (include TBI) and ABMI were recognized. Seventeen patients reached a total granulocyte count of >500 cells/mm3 within 4 weeks of ABMI (early graulocyte recovery), while seven patients required >4 weeks from ABMI (late granulocyte recovery). The time of platelet recovery (>50,000/mm3) was different for the groups with early and late granulocyte recovery (25 days vs. 54 days, p <.001). Six of seven patients with late granulocyte recovery received locl high-dose irratiation to >1/2 pelvis prior to bone marrow storage. Patients with late recovery did not tolerate maintenance chemotherapy. However, there was no difference in disease-free and overall survival, when compaing the groups with early and late granulocyte recovery. We conclude that these high-risk Ewing's sarcoma patients remain a poor-prognosis group in spite of intensive combined modality therapy include low-dose TBI. The control of microscopic systemic disease remains the major challenge to improving the cure rate. A new combined modality protocol with high-dose 'therapeutic' TBI (800 rad/2 fractions) is being used and the protocol design is outlined.
authors.affiliation: Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Kinsella
authors.forename: D
authors.initials: D
authors.lastname: Glaubiger
authors.forename: A
authors.initials: A
authors.lastname: Diesseroth
authors.forename: R
authors.initials: R
authors.lastname: Makuch
authors.forename: B
authors.initials: B
authors.lastname: Waller
authors.forename: P
authors.initials: P
authors.lastname: Pizzo
authors.forename: E
authors.initials: E
authors.lastname: Glatstein
mesh_terms: D000293:Adolescent; D000328:Adult; D000380:Agranulocytosis / Q000628:therapy; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D001859:Bone Neoplasms / Q000473:pathology / Q000628:therapy*; D002648:Child; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003609:Dactinomycin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D008297:Male; D009364:Neoplasm Recurrence, Local; D012512:Sarcoma, Ewing / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D014750:Vincristine / Q000008:administration & dosage; D014916:Whole-Body Irradiation
chemical_list: D003609:Dactinomycin; D014750:Vincristine; D003520:Cyclophosphamide